Introduction To Neuroscience - Final Exam

Introduction to Neuroscience - Final Exam

Spring, 2007

The final exam is based on the two attached papers. Questions about the two papers are to be answered separately. Prepare your answers using a word processor and print them out double-spaced, with your name on each part. Be sure to submit two separate sets of answers - staple the answers to Part A and Part B separately so the two profs. can both work on grading at the same time! We need hard copies, not electronically submitted files. Put your responses under Prof. Baird=s office door.

Consult your textbook, lecture notes, and any articles assigned for class in formulating your answer. There should be no need to use other material, although you may consult any other printed or web sources you wish. What you are forbidden to do is to discuss the exam with any other person in any way, before, during or after taking it, not even to say how much time you=re spending or how easy or hard it is.

In preparing your answers, do not include whole sentences or long phrases from the papers. We suggest taking notes and then not looking at the article while you=re writing, so your answer is in your own words.

Don=t worry about the statistics in the article - just focus on the concepts, methods, and results themselves.

We estimate that good answers could be given in 3-4 double-spaced pages for each of the two parts of the exam.

Your exam is due on ______day, May ___ by 4:00 p.m. Put it under the door of Professor Baird=s office in the Psychology department (Merrill 323). Part A - refer to Nomura et al., Mechanism of impairment of long-term potentiation by amyloid β is independent of NMDA receptors or voltage-dependent calcium channels in hippocampal CA1 pyramical neurons.

Some technical background

You are not expected to know or figure out the chemistry behind oligomers (several molecules stuck together in clumps) vs. fibrils (many molecules stuck together in lines). Just accept that amyloid β (Aβ) can exist in both of these forms, and that there is controversy about whether either or both have bad effects on neurons.

The electrophysiology in this paper was done by a slightly different method from what we discussed in the synaptic transmission classes in February and in our text, Chapter 5, but the difference isn=t important. Whereas the lectures and text refer to excitatory postsynaptic potentials (EPSPs), this paper refers to excitatory postsynaptic currents (EPSCs). This is just a technical difference in recording method that isn=t necessary to understand in detail. Instead of using intracellular micropipettes to pick up EPSPs, these authors used what are called Apatch pipettes@ and Awhole-cell recording@ which detects EPSCs. The important point is that both EPSPs and EPSCs are caused by the same phenomenon: excitatory synaptic input to a neuron. Your knowledge of EPSPs applies directly to EPSCs. One difference in how the responses look is the sign of the response: EPSPs go up (i.e. in the positive direction; e.g. Fig. 5.14c on p. 117 in our text), while EPSCs are negative-going when the cell is at normal resting potential (e.g. the traces in Fig. 1(B) in the paper). However, this is just the conventional way to show the responses - what gives rise to EPSPs and EPSCs is exactly the same: both are excitatory synaptic responses.

Calcium currents were measured using a bathing solution with barium ions (Ba) instead of calcium itself. This is a technical issue you don=t need to delve into here - it is the standard way of measuring Ca currents.

One other point of definition: Apaired pulse facilitation@ in the paper is the same as the facilitation referred to in our April 11 class.

Now, on to the questions! Each of the 4 questions on this part of the exam is worth 25 points. Suggested length: between 2 and 1 side of a page for each of the 4 questions, double-spaced.

1. This paper reports a negative result. Negative results can be important in science, but sometimes it is more difficult to have papers reporting negative findings accepted by journals than it is to have a paper accepted that reports positive effects. Explain why a good journal like Neuroscience Letters would have accepted this paper referring no effect of Aβ on NMDA receptors and calcium channels, whereas quite possibly the journal would have rejected a manuscript reporting no effect of Aβ on other receptors and channels. Specifically, compare this paper=s importance with a hypothetical paper reporting no effect of Aβ on leptin receptors and chloride channels. 2. Re: methods:

(a) On p.4, 2nd column, the authors say the cells were Aheld at +40 mV in the presence of CNQX@ (CNQX being an AMPA receptor antagonist) in order to measure specifically NMDA receptor contributions to the EPSC. Explain why this procedure would be expected to measure NMDA receptor responses specifically. (By the way, it is the fact that the cells were held at +40 mV instead of the normal resting potential that accounts for why the currents are positive-going in Fig. 3, rather than negative-going as in the traces in Fig. 1(B).)

(b) Explain why tetrodotoxin, TEA (tetraethylammonium, and 4-aminopyridine were included in the bathing solution when the authors measured calcium currents (p. 3, first column).

(c) Explain why the authors tested paired-pulse facilitation in this experiment. (Consider the problem of interpreting results if an experiment showed similar reductions in both LTP and facilitation, although that wasn=t the outcome here.)

3. Discuss how this paper is conceptually related to the paper by Jacobsen et al., the paper assigned for May 9. Consider especially the older hypothesis that the loss of memory in Alzheimer=s disease is caused by the death of neurons in the brain.

4. If neither NMDA receptor changes nor effects on calcium currents are the cause of the decrease in LTP produced by Aβ, what could be the mechanism by which Aβ acts? One possibility is mentioned in the discussion (2nd to last paragraph); discuss at least two other plausible specific processes involved in LTP that Aβ might target, and describe how one might go about testing each one.